Angiotensin II promotes remodelling-related events in cardiac fibroblasts.
Remodelling is a fundamental cardiac response to injury, and involves cardiac fibroblast proliferation and extracellular matrix production. Angiotensin II (A II) directly promotes these changes in cardiac fibroblasts, and is thus a critical element in cardiac hypertrophy and a processor of wound healing. Osteopontin mRNA was readily detectable in total RNA harvested from cultured neonatal and adult cardiac fibroblasts. Immunocytochemical staining of cultured adult cardiac fibroblasts grown on coverslips revealed the presence of beta 3 integrin on the surfaces of the cells. In the present study, we investigated the role of A II in a model of wound healing using floating collagen gels harboring adult rat cardiac fibroblasts. The presence of a monoclonal antibody against osteopontin, MPIIIB10, at 7.2 micrograms/ml, or the arginine-glycine-aspartate (RGD) peptide (10(-4) M), had no effect on gel contraction. Osteopontin itself induced fibroblast gel contraction (79.1 +/- 3.8%). But this effect of osteopontin was completely neutralized by MPIIIB10 (7.2 micrograms/ml), RGD peptide (10(-4) M), and monoclonal antibody against rat beta 3 integrin (25 micrograms/ml). These results suggest that A II promotes cardiac wound healing and remodelling processes by inducing osteopontin and beta 3 integrin in cardiac fibroblasts.
Nunohiro
T
T
Third Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Ashizawa
N
N
Graf
K
K
Do
Y S
YS
Hsueh
W A
WA
Yano
K
K
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D016023:Integrins / Q000502:physiology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D053495:Osteopontin; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000502:physiology; D014945:Wound Healing / Q000502:physiology*
D000911:Antibodies, Monoclonal; D016023:Integrins; D012333:RNA, Messenger; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D053495:Osteopontin; D000804:Angiotensin II